Hypercholesterolemia is known to be one of the prime risk factors of ischemic cardiovascular disease, such as arteriosclerosis. Bile acid sequestrants have been used to treat this condition; they seem to be moderately effective but they must be consumed in large quantities, i.e. several grams at a time and they are not very palatable.
Mevacor.RTM. (lovastatin), now commercially available, is one of a group of very active antihypercholesterolemic agents that function by limiting cholesterol biosynthesis by inhibiting the enzyme, HMG-CoA reductase. In addition to the natural fermentation products, mevastatin and lovastatin, there are a variety of semi-synthetic and totally synthetic analogs thereof.
The naturally occurring compounds and their semi-synthetic analogs have the following general structural formulae: ##STR2## wherein: Z is hydrogen, C.sub.1-5 alkyl or C.sub.1-5 alkyl substituted with a member of the group consisting of phenyl, dimethylamino, or acetylamino; and R is: ##STR3## wherein Q is ##STR4## R.sub.3 is H or OH; and
R.sup.2 is hydrogen or methyl; and a, b, c, and d represent optional double bonds, especially where b and d represent double bonds or a, b, c, and d are all single bonds, provided that when a is a double bond, ##STR5##
Japanese unexamined patent application J59-122,483-A describes antihypercholesterolemic compounds represented by the above general formula wherein R is ##STR6## R.sup.1 is methyl or hydrogen, R.sup.2 is hydrogen, halogen or lower alkyl, R.sup.3 is hydrogen, halogen or haloalkyl, and b and d represent optional double bonds.
Copending U.S. patent application Ser. No. 859,513 filed May 5, 1986 describes compounds of the above formula wherein R is ##STR7## wherein R.sup.6 is phenyl or substituted phenyl.
Copending U.S. patent application Ser. No 859,530 filed May 5, 1986 discloses compounds of the above formula wherein R is: ##STR8## wherein R.sup.6 is hydrogen or C.sub.1-5 alkyl.